POS0269 RESULTS OF ONE YEAR OBSERVATIONAL EXTENSION OF THE BRIDGE-PMR STUDY, A RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED TRIAL WITH RITUXIMAB IN POLYMYALGIA RHEUMATICA.
Authors: T. Bolhuis, D. Marsman, A. Den Broeder, N. Den Broeder, A. Van der Maas
Journal: Annals of the Rheumatic Diseases (2022)

Background Glucocorticoids (GC) are the cornerstone of treatment in Polymyalgia rheumatica (PMR) [1]. However, they are associated with considerable toxicity and inefficacy in part of the patients. Rituximab (RTX) was effective for PMR in a 21-week randomized controlled trial (RCT), however results from longer follow-up is still absent [2]. Objectives To assess, in a randomized double blinded fashion, the clinical and GC-sparing effects one year after RTX. Methods In the BRIDGE-PMR, an RCT of 38 recently diagnosed and 9 relapsing PMR (2012 EULAR/ACR classification criteria) patients recruited from the Sint Maartenskliniek, patients were randomly allocated in a 1:1 ratio and treated with 1x 1000mg RTX / placebo (PCB) iv, identical pre-medication and an accelerated GC tapering protocol. After the 21-week study, patients were assessed in a double blinded prospective extension study up to one year after infusion. The primary outcome at one year was between group difference in GC-free remission (PMR-activity score &lt; 10). Analysis was performed with Fischer’s exact test and a two-tailed p-value &lt; 0.05 was considered significant. Secondary outcomes were proportion of relapsing patients during the extension, proportion of patients with CRP &gt; 5mg/l during the extension, cumulative GC dose, DMARD use, EQ-5D score, and adverse events (AE). Results The proportion of patients in GC-free remission after one year was significantly higher in the RTX group (48%, 11/23) compared to the PCB group (17%, 4/24), with an absolute difference of 31% (95%-CI 6-56), a relative risk of 2.9 (95%-CI 1.1-7.7), p=0.03. The secondary outcomes showed statistically significant differences in RTX versus PCB in median GC cumulative dose: 1595 versus 2302 mg (p = 0.04) and median PMR-AS: 6 versus 15 (p = 0.02) (Table 1 and Figure 1). No differences were seen in other secondary outcomes. Table 1. Primary and Secondary Outcomes for Rituximab Versus Placebo Treatment One Year After Infusion Placebo [n=24] Rituximab [n=23] p-value Remission, number (%) 10 (42%) 15 (65%) 0.15 GC-free remission, number (%) 4 (17%) 11 (48%) 0.03 Cumulative GC dose 0-52 weeks, in mg 2302 (1595 - 2881) 1595 (1275 – 2260) 0.04 Cumulative GC dose 21-52 weeks, in mg 959 (91 – 1442) 160 (0 - 902) 0.10 Relapse patient 21-52 weeks, number (%)* 14 (58%) 12 (52%) 0.77 PMR-AS** 15.25 (7.75 - 22.5) 6.3 (4.7 - 12.1) 0.02 CRP serum level, in mg/L 3.5 (2 - 5) 3 (1 - 4) 0.29 physicians’ VAS, 0-10 2 (0.2 - 3.7) 1 (0 - 2) 0.08 Morning stiffness, in minutes 25 (4 - 60) 10 (0 - 30) 0.06 VAS pain, 0-10 3 (1.45 - 6.4) 1.8 (0.7 - 5) 0.16 EQ5D-5L, score at week 52# 0.71 (0.65 – 0.77) 0.71 (0.63 – 0.77) 0.87 EQ5D-5L, change week 21-52# 0 (-0.03 - 0.09) 0.07 (-0.05 - 0.10) 0.56 Methotrexate use, number (%) 4 (17%) 2 (9%) 0.67 Adverse events, total, % of patients 8, 26% 6, 33% 0.75 Notes . * Relapse was defined as therapy intensification, based on either a) an increase in oral prednisolone, b) adding intramuscular methylprednisolone, or c) starting or switching a DMARD due to treatment inefficiency ** Remission is based on the PMR-AS, calculated by CRP +VASp +VASph + (MST *0.1) + EUL, and a PMR-AS &lt; 10 was considered remission or low disease-activity. # Number of patients for placebo versus RTX were n=23 versus n=23 respectively at week 52, and for comparison of change between week 21-52 total number of patients were n=21 versus n=23 respectively Figure 1. Cumulative GC Dose 0-52 Weeks, in mg Conclusion Efficacy of 1x1000 mg RTX in PMR was maintained up to 1 year follow-up, while also demonstrating a GC sparing effect. A larger trial, also assessing effect of on demand retreatment, is needed to confirm our results, and provide insight in which patients most likely benefit from RTX. References [1]Dejaco C, et al. Ann Rheum Dis 2015;74(10):1799-807. doi: 10.1136/annrheumdis-2015-207492 [2]Marsman DE, et al. The Lancet Rheumatology 2021;3(11):e758-e66. doi: 10.1016/S2665-9913(21)00245-9 Disclosure of Interests None declared